| Literature DB >> 34112699 |
Peter Horak1,2, Christoph Heining3,4,5, Simon Kreutzfeldt1,2, Barbara Hutter6,7, Andreas Mock1,2,8, Jennifer Hüllein6, Martina Fröhlich6,7, Sebastian Uhrig6,7, Hanno Glimm9,4,5, Stefan Fröhling10,2, Arne Jahn4,5,11, Andreas Rump4,5,11, Laura Gieldon11,12, Lino Möhrmann3,4,5, Dorothea Hanf3,4,5, Veronica Teleanu1,2,13, Christoph E Heilig1,2, Daniel B Lipka1,2, Michael Allgäuer14, Leo Ruhnke3,4,5, Andreas Laßmann1, Volker Endris14, Olaf Neumann14, Roland Penzel14, Katja Beck1,2, Daniela Richter3,4,5, Ulrike Winter1,2, Stephan Wolf2,15, Katrin Pfütze2,16, Christina Geörg2,16, Bettina Meißburger2,16, Ivo Buchhalter17, Marinela Augustin18, Walter E Aulitzky19, Peter Hohenberger20,21, Matthias Kroiss22,23,24, Peter Schirmacher2,14, Richard F Schlenk2,8,13,25, Ulrich Keilholz26,27, Frederick Klauschen27,28, Gunnar Folprecht5,29, Sebastian Bauer30,31, Jens Thomas Siveke31,32,33, Christian H Brandts34,35,36,37, Thomas Kindler38,39,40, Melanie Boerries41,42,43, Anna L Illert41,43,44, Nikolas von Bubnoff44,45, Philipp J Jost46,47,48, Karsten Spiekermann48,49, Michael Bitzer50,51, Klaus Schulze-Osthoff51,52, Christof von Kalle53, Barbara Klink4,5,11,54,55, Benedikt Brors2,7, Albrecht Stenzinger2,14, Evelin Schröck4,5,11, Daniel Hübschmann2,6,56, Wilko Weichert48,57.
Abstract
The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patients (31.8%) and resulted in significantly improved overall response and disease control rates (23.9% and 55.3%) compared with previous therapies, translating into a progression-free survival ratio >1.3 in 35.7% of patients. These data demonstrate the benefit of molecular stratification in rare cancers and represent a resource that may promote clinical trial access and drug approvals in this underserved patient population. SIGNIFICANCE: Rare cancers are difficult to treat; in particular, molecular pathogenesis-oriented medical therapies are often lacking. This study shows that whole-genome/exome and RNA sequencing enables molecularly informed treatments that lead to clinical benefit in a substantial proportion of patients with advanced rare cancers and paves the way for future clinical trials.See related commentary by Eggermont et al., p. 2677.This article is highlighted in the In This Issue feature, p. 2659. ©2021 American Association for Cancer Research.Entities:
Mesh：
Year: 2021 PMID： 34112699 DOI： 10.1158/2159-8290.CD-21-0126
Source DB: PubMed Journal: Cancer Discov ISSN： 2159-8274 Impact factor: 39.397